1. Field of the Invention
The present invention relates generally to plastic medical instruments and devices having improved blood compatibility and, specifically, to devices having improved thromboresistant properties for the prevention of formation of harmful thrombi in the presence of blood or blood products.
2. Description of the Prior Art
Medical plastic materials which directly contact blood or blood products are required to possess blood compatibility and biocompatibility, as well as certain mechanical properties including flexibility, elasticity and durability. At present there are many types of medical instruments or devices requiring antithrombotic and thus hemocompatible surface properties. Examples include the arterial graft, artificial heart, heart-lung machine, pacemaker, artificial heart valve, vascular graft tubing, and intra-aortic balloon. When blood comes in contact with such materials foreign to the human body a number of processes result, including fibrin production and platelet activation. Each activated platelet tends to adhere to adjacent platelets thus forming aggregates. Each clump of platelets, with interwoven strands of fibrin, makes up a "thrombus." Thrombus formation is quite dangerous because it can obstruct the flow of blood to vital organs causing stroke or death.
One prior art technique for addressing the problem of fibrin production and platelet activation has been the periodic administration of antithrombotic agents to the patient orally or by intravenous injection. This technique is inconvenient because the treatment has only a short-term beneficial effect and must soon be repeated. Also, while the formation of thrombi may be reduced, the pharmacological action spreads over the whole body and adverse side effects may result.
Because of the drawbacks of oral or intravenous administration of antithrombotic agents, various coating techniques have also been attempted. A heparin coating on a medical device can give it short-term hemocompatibility, but heparin tends to wash away in the blood because of its water solubility. Covalently bound heparin has more permanence but any type of internal heparinized surface may lead to thrombocytopenia (J. E. Nelson, Arch. Intern. Med., 138, 548 (1978)).
Another approach to hemocompatibility is the use of a polyethylene oxide surface coating which prevents platelet attachment. However, this type of coating repels cell overgrowth, making it unsatisfactory for use on vascular grafts or coronary stents, which are intended to attract cell overgrowth.
One technique used for conferring long-term hemocompatibility involves encouraging the growth of a layer of endothelial cells over the surface of the implanted device. Such growth occurs after first immobilizing extracellular matrix (ECM) proteins on the surface of the device. However, cell overgrowth is a rather slow process even on a prepared surface. In one study, for example, an expanded polytetrafluoroethylene graft required 180 days to attain 96 percent of cell overgrowth coverage.
It has also been found that some degree of hemocompatibility results from a surface coating of immobilized phosphorylcholine. Another approach to hemocompatibility is the use of albumin-binding coatings, since albumin is known to inhibit fibrinogen adsorption in vitro and in vivo. Coatings containing plasminogen activators such as polysine, streptokinase, and urokinase are also known to inhibit clotting, since activated plasminogen dissolves fibrin as it forms.
Despite these advances in the art, a need exists for a simplified technique for rendering plastic medical devices of the above type thromboresistant, which technique is reliable, cost effective and which can be easily performed with commonly available starting materials.
Accordingly, it is an object of the present invention to provide a simple process for the manufacture of plastic medical instruments and devices having properties which resist thrombus formation and the activation of platelets which would otherwise degrade the functions of medical instruments and devices or lead to the manifestation of complications in the living body.